The overall goal of this project is to understand the role of histidinerich proteins (HRPs) present in human parotid and submandibular secretions in the non-immune oral defense systems. Recent work has shown that a group of at least 7 HRPs in glandular secretions which display a genetic polymorphism, exhibit both antibacterial and antifungal properties. We have isolated, purified and determined the primary structure of one of these components. This protein was found to be a potent inhibitor of Candida albicans germination. While oral candidal infections in healthy individuals are rare, they are a more serious health problem in patients debilitated by a variety of conditions. Since the population of patients susceptible to candidosis is increasing, the investigation of biological agents with anticandidal activity in the oral cavity is of considerable interest. The specific aims of this project are to: 1. Isolate and characterize the individual HRPs from human paratid and submandibular secretions. 2. Determine the primary structure of the individual HRPs. 3. Elucidate the biosysthetic relationship among HRPs and determine the molecular basis of their genetic polymorphism using recombinant DNA technology. 4. Characterize the antimicrobial properties of HRPs against selected oral fungal and bacterial strains. 5. Determine the concentration range of HRPs under stimulated and non-stimulated conditions in salivary secretions and in whole saliva of healthy subjects.